Sterilization, pasteurization and disinfection are essential for medical materials which contact directly or indirectly with living tissues. Various methods of sterilization, pasteurization and disinfection have been proposed and it is well known that either one of them is employed depending on properties of medical materials and purposes of use thereof and efforts have been made to ensure and accomplish safety and innocuousness of materials.
Among these methods, advantages of .gamma.-ray sterilization method are noticed in that the method can sterilize the materials through container in which the materials are completely enclosed and besides the method is effective for bacterial spores high in heat resistance and further Pseudomonas aeruginosa, spores of tubercle bacillus and Gram-negative bacteria which often show resistance against medicines (disinfectants) and the .gamma.-ray sterilization method is considered to have high reliability in sterilization of rubber articles and plastic articles (general polymer materials poor in heat resistance) to which is difficult to apply high pressure steam sterilization method and dry sterilization method.
As the method which comprises enclosing a non-heat resistant material in a container made of plastic film and then sterilizing the material through the container, gas sterilization method with ethylene oxide is famous and is widely used in hospitals and medical device makers. In this case, it is necessary to perform desorption of residual gas adsorbed to materials carefully and over a long period of time and further to keep watch to ensure that amount of still remaining ethylene oxide (and ethylene glycol, ethylene chlorohydrin, etc. as modification components thereof) is less than permissible limits. Especially, when this gas sterilization method is applied to sterilization of hydrogels (water-containing gels) represented by polyacrylamide, much care must be taken for discharge of a large amount of gas dissolved in water as well as adsorbed gas. Although it can be said that regulation value can be met (degassing to 2000 ppm), there is some fear of remaining toxicity which may cause hemolysis and thrombus.
.gamma.-ray sterilization method does not require operation for removal of residual toxin as required in the above gas sterilization method and disinfection with chemicals (ethyl alcohol, formalin, glutaraldehyde, chlorohexidine, benzalkonium chloride, etc.) and hence, merits as sterilization method for non-heat resistant medical materials have been widely recognized. However, it has been warned that irradiation of a large quantity of .gamma.-ray results in denaturation (radical decomposition and oxidation decomposition of materials) of most of rubbers and plastics to produce soluble (water-soluble) low molecular weight deterioration products and furthermore, mechanical strength of the materials per se often decreases. (Takuma Ohba; "Kobunshi", 22, 607 (1973)).
The phenomena of formation of radicals due to irradiation with .gamma.-ray, which cause deterioration by oxidation in which coexisting oxygen participates have been confirmed in natural polymers (protein) and synthetic polymers and aqueous solutions of these polymers. [See, P. S. Elias et al (translators, Rikimaru Hayashi et al); "Shokuhin Shosya no Kagaku" ("Chemistry of Irradiation of Food", p. 11 (1981) published from Gakkai Shuppan Center; Mineo Sado, "Ikishi" (J. Medical Instruments) 55, 480 (1985); and Kenji Sato, "Rinshoishi" (J. Clinics), 11, 422 (1985)]. Further, it was attempted to conduct irradiation without oxygen (air) (in nitrogen atmosphere) in order to avoid deterioration due to oxidation, but this also results in considerable deterioration and denaturation (due to radical decomposition) of both protein and synthetic polymer and besides there is a tendency of increase in .gamma.-ray resistance of microorganisms in nitrogen atmosphere and irradiation of larger quantity of .gamma.-ray for complete sterilization promotes radical decomposition of materials.
Considering these problems, irradiation dosage necessary and sufficient and minimum for accomplishing the purpose of sterilization and confining decomposition of materials to the minimum (permissible limit) has been searched and sterilization effect with dosage of 0.6-2.5 Mrad has been investigated, for example, on pad (0.76-1.1 Mrad) and catheter, injection cylinder, surgical suture, dialyser for kidney dialysis, infustion set and glove (2-2.5 Mrad). Thus, since generally deterioration (decomposition) of materials is accelerated with increase of irradiation dosage, it has been guided to decrease initial number of living bacteria (before sterilization) as small as possible and to keep .gamma.-ray dosage at less than 2.5 Mrad. [See, Takuma Ohba, "Kogyo Zairyo" (Industrial Materials), 25 (2), 65 (1977); "Kobunshi" (Polymer), 22, 607 (1973); Kenji Sato, "Rinshoishi" (J. Clinics), 11, 422 (1985); Mineo Sado, "Gosei Jushi" ("Synthetic Resin" 31, (5), 12 (1985); Fumio Yoshii et al, "Ikishi" (J. Medical Instruments), 55, 251 ( 1985); and Yoshio Iwasaki et al, "Ikishi" (J. Medical Instruments), 55, 244 (1985)].
On the other hand, as hydrogel innocuous for living organisms, there have been proposed a gel obtained by freezing and thawing aqueous polyvinyl alcohol solution and a gel obtained by partial dehydration in vacuo of aqueous polyvinyl alcohol solution as it is in frozen state. These gels are expected to be useful as supplement (for prevention of adhesion) for defects in lung thymus, pericardium, duramater and artificial trachea, artificial gullet, artificial cartilage, electrodes for embedding ocular conjunctiva and cornea, membranes for preventing adhesion of tendon, materials for suture of sclera, electrodes for artificial internal ear, denture-base, supplement for upper and lower jaws, membrances for preventing adhesion of joints, catheters for gullet, rectum and vagina. [See "NMR Igaku" (NMR Medical Science) 5 (2), 85 (1985); "Am. J. Ophthalmology", 100, 328 (1985) and 99, 492 (1985)].
As process for producing such polyvinyl alcohol hydrogels, for example, Japanese Patent Kokoku No. 47-12,854 and Japanese Patent Kokai Nos. 59-56,446 and 60-177,066 disclose frozen and thawed gels and Japanese Patent Kokai Nos. 57-130,543 and 58-36,630 disclose gels obtained by partial dehydration in vacuo in the frozen state. These hydrogels are obtained as insoluble rubbery materials with mechanical strength and flexibility similar to flexible tissues of living organisms by subjecting aqueous polyvinyl alcohol solution to merely freezing and thawing or freezing, keeping in vacuo and thawing without any chemical treatments. These are specific hydrogels which are highly inert to living tissues and do not cause reaction with foreign materials, infiltration into cells, inflammation and stimulus and which can function as a substitute for gullet when implanted in the gullet which is considered to be strongest in elimination action among various organs. However, since these hydrogels do not undergo chemical crosslinking and have rubbery state merely by crystallites supposed to be produced at interlocking points of polymer in the production step ["Kobunshi Kako" (Polymer processing), 32, 523 (1983)], heat resistance cannot be expected and both the high pressure steam sterilization and the dry sterilization cannot be applied thereto. Further, they contain a large amount of water and so it is difficult to release the remaining dissolved gas after gas sterilization.
Thus, .gamma.-ray sterilization method is naturally expected. However, it has been found that when this hydrogel is irradiated with .gamma.-ray of the aforesaid target value (2.5 Mrad or less), considerable amount of water-soluble deterioration products are by-produced. That is, there have been experienced many cases where content of soluble matters (decomposition products) in the gel is as high as 0.02-0.03 wt % according to analysis (KMnO.sub.4 titration) of warm water extracts based on standard for medical artificial vessel (Notification No. 298 of the Welfare Ministry). The amount of soluble matters reduces to 1/3-1/100 with decrease in irradiation dosage of .gamma.-ray to 0.1-0.2 Mrad, but it is impossible to surely accomplish the sterilization by the irradiation dosage of less than 0.3 Mrad.